Association of HLA-alleles with the immune regulation of chronic viral infections

Int J Biochem Cell Biol. 2012 Aug;44(8):1361-5. doi: 10.1016/j.biocel.2012.05.003. Epub 2012 May 14.

Abstract

Cytotoxic CD8 T lymphocytes (CTLs) have an astonishing ability to eliminate pathogen-infected cells. However, if uncontrolled, these CTLs could cause devastating pathology to host tissues. CD8(+) effector T cells, therefore, interact with antigen-presenting cells and other immune cells, such as regulatory T cells (Tregs), to regulate further on-site expansion and differentiation of the effector cells. This ensures protection of the host with minimal bystander pathological consequences. During prolonged chronic infections CTLs, however, often lose effector function. Induction of multiple inhibitory pathways is emerging as a major regulator converting effector CTLs into exhausted CTLs during chronic viral infections such as HIV, HCV and HBV. The mechanisms involved in induction of exhaustion during chronic viral infections are the focus of this article. Blockade of inhibitory pathways could potentially restore functional capabilities to exhausted CTLs and represents a potential immune-based intervention in chronic viral infections.

Publication types

  • Review

MeSH terms

  • Alleles
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Chronic Disease
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Humans
  • Models, Immunological
  • Signal Transduction / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Virus Diseases / immunology*

Substances

  • HLA Antigens